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BioAssay: AID 219982

Susceptibility to be hydrolysed by a partially purified cAMP phosphodiesterase from rabbit kidney

The synthesis of certain new 8-(arythio)- and 8-(alkylthio)-cAMP derivatives and N6-alkyl- and N6-dialkyl-8-(arylthio) and -8-(alkylthio) derivatives of cAMP is reported. On the basis of activation of protein kinase, several N6-alkyl-8-(benzylthio)-cAMP derivatives were selected for evaluation as inotropic agents using cat papillary muscle in vitro. Activity in these studies resulted in the more ..
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 Tested Compounds
 Tested Compounds
All(70)
 
 
Unspecified(70)
 
 
 Tested Substances
 Tested Substances
All(70)
 
 
Unspecified(70)
 
 
 Related BioAssays
 Related BioAssays
AID: 219982
Data Source: ChEMBL (217322)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-21
Modify Date: 2014-05-19

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Tested Compounds:
Description:
Title: Synthesis and enzymatic and inotropic activity of some new 8-substituted and 6,8-disubstituted derivatives of adenosine cyclic 3',5'-monophosphate.

Abstract: The synthesis of certain new 8-(arythio)- and 8-(alkylthio)-cAMP derivatives and N6-alkyl- and N6-dialkyl-8-(arylthio) and -8-(alkylthio) derivatives of cAMP is reported. On the basis of activation of protein kinase, several N6-alkyl-8-(benzylthio)-cAMP derivatives were selected for evaluation as inotropic agents using cat papillary muscle in vitro. Activity in these studies resulted in the selection of several analogues for in vivo studies in the anesthetized dogs. The best inotropic agent selected on the basis of in vivo studies was N6-butyl-8-(benzylthio)-cAMP (26), which exhibited an increase in blood-flow rate of 85% with no increase in heart rate. A large-scale synthesis of 26 from cAMP is reported via N1-alkylation, followed by a Dimroth rearrangement, reduction, bromination, and nucleophilic displacement via benzyl mercaptan. The N6-alkyl-8-substituted-cAMP derivatives represent a new class of potent inotropic agents. The direct mechanism of action of 26 suggests the possible utility of this cyclic nucleotide to treat clinical myocardial infarction by rapid intravenous infusion.
(PMID: 6245211)
Comment
Putative Target:

ChEMBL Target ID: 104679
Target Type: PROTEIN FAMILY
Pref Name: Phosphodiesterase 4
Synonyms: cAMP-specific 3';5'-cyclic phosphodiesterase 4C;DPDE1;PDE21;cAMP-specific 3';5'-cyclic phosphodiesterase 4A;DPDE2;PDE46;cAMP-specific 3';5'-cyclic phosphodiesterase 4D;DPDE3;PDE43;cAMP-specific 3';5'-cyclic phosphodiesterase 4B;DPDE4;PDE32;
Gene Name: DPDE1;PDE4C;DPDE2;PDE4A;DPDE3;PDE4D;DPDE4;PDE4B;
Protein Accession: Q08493;P27815;Q08499;Q07343;
Protein GI: 20141263;116242706;12644392;729163;
Organism: Homo sapiens
Tax ID: 9606
Target Classification 1: enzyme phosphodiesterase pde_4 pde_4a
Target Classification 2: enzyme phosphodiesterase pde_4 pde_4b
Target Classification 3: enzyme phosphodiesterase pde_4 pde_4c
Target Classification 4: enzyme phosphodiesterase pde_4 pde_4d
Confidence: Multiple homologous protein targets may be assigned
Relationship Type: Homologous protein target assigned
Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Hydrolysis activity commentHydrolysis activity commentString
2Hydrolysis standard flagHydrolysis standard flagInteger
3Hydrolysis qualifierHydrolysis qualifierString
4Hydrolysis published valueHydrolysis published valueFloat
5Hydrolysis standard valueHydrolysis standard valueFloat

Data Table (Concise)
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